Synergistic anti-cd47 therapy for hematologic cancers

Abstract

Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.

What is claimed is: 
     
         1 . A method for the treatment of a hematologic cancer in a patient, the method comprising:
 administering to said patient a synergistic combination of agents comprising a first agent that selectively inhibits or blocks CD47 and a second agent that selectively inhibits or blocks a second cancer associated cell surface marker.   
     
     
         2 . The method of  claim 1 , wherein the first agent is an antibody selective for CD47. 
     
     
         3 . The method of  claim 2 , wherein the second agent is an antibody selective for a cell surface marker. 
     
     
         4 . The method of  claim 3 , wherein one or both of said antibodies is conjugated to a cytotoxic agent. 
     
     
         5 . The method of  claim 4 , wherein said cytotoxic agent is selected from the group consisting of a radioactive isotope, a chemotherapeutic agent and a toxin. 
     
     
         6 . The method of  claim 3 , wherein the hematologic cancer is acute myelogenous leukemia. 
     
     
         7 . The method of  claim 6 , wherein said second marker is selected from CD33;
 CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.   
     
     
         8 . The method of  claim 3 , wherein the hematologic cancer is non-Hodgkin's lymphoma (NHL). 
     
     
         9 . The method of  claim 8 , wherein the NHL is a diffuse large B cell lymphoma. 
     
     
         10 . The method of  claim 9 , wherein said second marker is selected from CD20 and CD22. 
     
     
         11 . The method of  claim 3 , wherein the hematologic cancer is a chronic lymphocytic leukemia. 
     
     
         12 . The method of  claim 10 , wherein the second marker is selected from CD20, CD22 and CD52. 
     
     
         13 . The method of  claim 1 , wherein the first and second agents are comprised in a bispecific antibody selective for CD47 and for a second cancer associated cell marker. 
     
     
         14 . A multispecific antibody specific for CD47 and for a cell surface marker associated with a hematologic cancer. 
     
     
         15 . The multispecific antibody of  claim 14 , wherein said cell surface marker is selected from CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2. 
     
     
         16 . The multispecific antibody of  claim 15 , wherein the antibody is humanized or chimeric.